It is known that the function of the tear film is that of keeping the ocular surface wet, protecting the corneal and conjunctival epithelium and transporting biologically active substances which are useful for the physiology of the eye (nutrients, oxygen). To preserve the physical characteristics of the ocular epithelium, the tear film must have a proper surface tension (proper capacity of the mucous layer to permits the aqueous phase to be extended on the epithelium) and must have a physiological evaporation speed. The alteration of these properties determines the rise of ocular dryness and possibly dry eye syndrome.
The tear film is substantially composed of three layers. The first adheres to the ocular surface (cornea, conjunctiva) and is mainly composed of mucin; the intermediate layer is substantially composed of an aqueous solution containing ions, proteins etc.; the third layer, in contact with the air, is mainly composed of non-polar and polar lipids of different nature (cholesterol, cholesterol esters, phospholipid triglycerides, ceramides, cerebrosides etc.) having the function of avoiding a sudden evaporation of the intermediate aqueous layer.
In reality, such layers are in dynamic equilibrium with each other, due to the eyelid blinking, which causes an overall more complex and homogenous tear film.
One cause of the onset of ocular dryness and in particular of dry eye is the excessive evaporation of the aqueous layer of the tear film caused by a poor functionality of the outer lipid layer following qualitative-quantitative modifications of its composition.
Ophthalmic compositions are on the market containing polymers which reduce the evaporation of the tear film due to a certain viscosity level.
Other compositions based on phospholipids or oil emulsions in water are used in order to restore the natural lipid layer of the tear film, always with the function of reducing the evaporation of the aqueous film. These compositions are for instance reported in the Glonek patent, U.S. Pat. No. 5,578,586.
In particular, the aforesaid patent describes a specific and metastable formulation, composed of a phospholipid component and an oily component, at determined concentrations and ratios thereof emulsified in water.
In the indicated patent, the phospholipid component is composed of charged phospholipids (net positive or negative charge) in quantities in the range of 0.01%-7% by weight on the total weight of the composition, while the oily component is composed of mineral oils in quantities between 0.1%-12.5% by weight on the total weight of the composition.
The patent specifies, in particular, that this oil type, defined “non-polar”, is preferred to that of animal or vegetal origin, defined “polar” (since they contain a significant number of acid and/or ester groups), since the latter would cause undesired effects of sight dimming and composition instability with respect to synthetic oils.
It should be noted that, with regard to the phospholipids, zwitterionic molecules such as phosphatidylethanolamine and phosphatidylcholine (lecithin) are explicitly excluded from the scope of U.S. Pat. No. 5,578,586, since they are provided with a positive charge which, at pH 7, cancels the negative charge of the phosphate group. Negatively-charged phospholipids are preferred according to this patent, as the negative charge which they impart would facilitate, by a light electrostatic repulsion with the ocular surface negatively-charged, the extension of the composition on the ocular surface.
Moreover, all formulations containing lipids which are available on the market today require being preserved at low temperature (4° C.) due to the poor stability of the lipid component which grows rancid at room temperature.